As one of the most aggressive human tumors, pancreatic cancer (PC) is accompanied by poor treatment and prognosis. Although emerging evidence has highlighted the importance of long noncoding RNAs in multiple cancers, the specific regulatory roles mostly remain obscure. Our aim was to disclose the role of CERS6 antisense RNA 1 (CERS6-AS1) in PC.
Quantitative real-time polymerase chain reaction analysis was used to examine the expression of CERS6-AS1 in PC cell lines. Western blot analysis was used to assess the protein levels of high-mobility group AT-hook 1 (HMGA1). Colony formation, 5-ethynyl-20-deoxyuridine, transwell, and wound healing assays were performed to detect the functions of CERS6-AS1 on PC development. In addition, RNA pull-down, RNA immunoprecipitation, and luciferase reporter assays were implemented to delve into the regulatory mechanism of CERS6-AS1 in PC.
CERS6-AS1 was significantly upregulated in PC. CERS6-AS1 silence obviously inhibited cell proliferation and migration in PC. Furthermore, CERS6-AS1 sponged microRNA-15a-5p (miR-15a-5p) and microRNA-6838-5p (miR-6838-5p) to regulate HMGA1. Moreover, rescue assays verified that CERS6-AS1 was involved in cell proliferation and migration in PC via targeting miR-15a-5p/miR-6838-5p/HMGA1 axis.
CERS6-AS1 enhanced HMGA1 expression to contribute to the progression of PC by sequestering miR-15a-5p and miR-6838-5p.
CERS6-AS1 enhanced HMGA1 expression to contribute to the progression of PC by sequestering miR-15a-5p and miR-6838-5p.This study aimed to evaluate the effect of vagotomy, when associated with splenectomy, on adiposity and glucose homeostasis in Wistar rats.
Rats were divided into 4 groups vagotomized (VAG), splenectomized (SPL), VAG + SPL, and SHAM. Glucose tolerance tests were performed, and physical and biochemical parameters evaluated. Glucose-induced insulin secretion and protein expression (Glut2/glucokinase) were measured in isolated pancreatic islets. Pancreases were submitted to histological and immunohistochemical analyses, and vagus nerve neural activity was recorded.
The vagotomized group presented with reduced body weight, growth, and adiposity; high food intake; reduced plasma glucose and triglyceride levels; and insulin resistance. The association of SPL with the VAG surgery attenuated, or abolished, the effects of VAG and reduced glucose-induced insulin secretion and interleukin-1β area in β cells, in addition to lowering vagal activity.
The absence of the spleen attenuated or blocked the effects of VAG on adiposity, triglycerides and glucose homeostasis, suggesting a synergistic effect of both on metabolism. The vagus nerve and spleen modulate the presence of interleukin-1β in β cells, possibly because of the reduction of glucose-induced insulin secretion, indicating a bidirectional flow between autonomous neural firing and the spleen, with repercussions for the endocrine pancreas.
The absence of the spleen attenuated or blocked the effects of VAG on adiposity, triglycerides and glucose homeostasis, suggesting a synergistic effect of both on metabolism. The vagus nerve and spleen modulate the presence of interleukin-1β in β cells, possibly because of the reduction of glucose-induced insulin secretion, indicating a bidirectional flow between autonomous neural firing and the spleen, with repercussions for the endocrine pancreas.Up to 15% of pancreatic cancer is hereditary. We aim to study the prevalence of pathogenic germline variants (PGVs) in patients referred for genetic counseling with a family history (FH) of pancreatic cancer.
We performed a retrospective single institution cohort study of individuals who underwent cancer genetic counseling with a FH of pancreatic cancer.
We identified 314 patients. Genetic testing was performed in 291 (92.7%) and 187 (59.6%) underwent expanded multigene panel testing. Fifty-four PGVs were found in 53 (16.9%) individuals; PGVs in BRCA1/2 (37%) were most common. Seventy-two variants of uncertain significance (VUS) were found in 58 (18.5%) individuals; VUS in ATM (16.7%) were the most common. Of the 112 (35.4%) with a first-degree family member with pancreatic cancer, 14 PGVs were identified in 14 (12.5%) individuals and 28 VUS were identified in 21 (18.8%) individuals. After genetic testing, 47 (15.0%) individuals met International Cancer of the Pancreas Screening criteria and 67 (21.3%) met American College of Gastroenterology criteria for pancreatic surveillance.
Genetic testing of individuals with a FH of pancreatic cancer represents an opportunity to identify individuals who may be candidates for pancreatic surveillance.
Genetic testing of individuals with a FH of pancreatic cancer represents an opportunity to identify individuals who may be candidates for pancreatic surveillance.To compare the treatment outcomes of gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX; a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) for metastatic pancreatic cancer.
We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with GnP or mFFX as the first-line chemotherapy between March 2014 and December 2019 in our hospital. Treatment outcomes were compared using propensity score matching to adjust for age, sex, performance status, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, and disease status (metastatic or recurrent).
Five hundred sixty-eight patients were included (GnP/mFFX, 456/112). After propensity score matching, 218 patients were extracted. The median age was around 61 years, and the proportion of performance status 0 was approximately 90%. https://www.selleckchem.com/products/pf-04965842.html The median overall survival values were 14.6 and 15.5 months (P = 0.45), and the median progression-free survival was 7.4 months (P = 0.53) for GnP and mFFX, respectively. The disease control rates were higher in the GnP group (82.6% vs 67.9%, P = 0.02). In nonhematologic adverse events, grade 3/4 anorexia and diarrhea occurred significantly more frequently in the mFFX group.
Gemcitabine with nab-paclitaxel had a higher disease control rate and lower rates of severe anorexia and diarrhea in our propensity-matched population.
Gemcitabine with nab-paclitaxel had a higher disease control rate and lower rates of severe anorexia and diarrhea in our propensity-matched population.